1. Field of the Invention
The present invention relates to 5-substituted-isoxazole-4-carboxamide derivatives, to their use as antiinflammatory and antiarthritic agents, to their use as intermediates, and to pharmaceutical compositions containing them.
2. Description of Background Art
Isoxazole-4-carboxylic acid derivatives have been reported in the following references as having antiinflammatory and/or antiarthritic activities:
(a) U.S. Pat. No. 4,087,535 discloses 5-methylisoxazole-4-carboxylic acid anilides of formula (I) ##STR2## wherein R.sup.1, R.sup.2, and R.sup.3 may each be for example C.sub.1-3 alkyl or C.sub.1-3 alkoxy where the alkyl portions may be substituted with one or more halogen atoms; R.sup.1 and R.sup.2 may additionally be a hydrogen atom in which case R.sup.3 is not methyl. U.S. Pat. No. 4,284,786 discloses the specific compound 5-methyl-isoxazole-4-carboxylic acid, 4-(trifluoromethyl)anilide, i.e. compound of formula (I) wherein R.sup.1, R.sup.2 are each H, and R.sup.3 is 4-trifluoromethyl.
(b) British Pat. No. 1,596,383 discloses 5-methylisoxazole-4-carboxamides of formula (II) ##STR3## wherein Het represents an unsaturated heterocyclic radical opt. substituted with e.g. alkyl, alkoxy, or halogen.
(c) European Patent Application No. 12,435 discloses isoxazole-4-carboxamides of formula (III) ##STR4## wherein R.sup.1 is H, alkyl, or haloalkyl; R.sup.2 is H or alkyl; R.sup.3 is H or halogen; U is --CH-- or nitrogen; and W is oxygen or carbonyl; or W is a direct bond in which case, R.sup.1 is methyl, R.sup.2, R.sup.3 are each H, and U is --CH--.
(d) U.S. Pat. No. 4,284,785 discloses isoxazole-4-carboxylic acid esters and thioesters of formula (IV) ##STR5## wherein X is oxygen or sulfur; R.sup.1 is C.sub.1-4 alkyl; and Ar represents phenyl opt. substituted with one or more groups selected from halogen, C.sub.1-4 alkyl, C.sub.1-4 alkoxy, trifluoromethyl and trichloromethyl. These compounds are useful as intermediates in the preparation of corresponding antiinflammatory .beta.-ketopropionitriles. Two compounds of formula (IV) wherein R.sup.1 is CH.sub.3, X is oxygen, and Ar is 4-methoxyphenyl or 2,4,6-trichlorophenyl also exhibit antiinflammatory activity.
(e) German Offenlegunsschrift No. 3,247,454 discloses 3-phenyl-5-methylisoxazole-4-carboxylic acid anilides of formula (V) ##STR6## wherein R.sup.1 is H, Cl, or F; R.sup.2 is H or methyl; and R.sup.3 is Cl, methyl, or trifluoromethyl.
5-Cyclohexyl-3-methylisoxazole-4-carboxamide (VI) has been prepared but no biological activity was reported therein (J. Chem. Soc., 1963, p 5845). ##STR7##